Comparison of the basic morphology and function of 3D lung epithelial cultures derived from several donors.
Curr Res Toxicol
; 1: 56-69, 2020 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-34345837
In vitro models of the human lung play an essential role in evaluating the toxicity of inhaled compounds and understanding the development of respiratory diseases. Three-dimensional (3D) organotypic models derived from lung basal epithelial cells and grown at the air-liquid interface resemble human airway epithelium in multiple aspects, including morphology, cell composition, transcriptional profile, and xenobiotic metabolism. Whether the different characteristics of basal cell donors have an impact on model characteristics and responses remains unknown. In addition, studies are often conducted with 3D cultures from one donor, assuming a representative response on the population level. Whether this assumption is correct requires further investigation. In this study, we compared the morphology and functionality of 3D organotypic bronchial and small airway cultures from different donors at different weeks after air-lift to assess the interdonor variability in these parameters. The thickness, cell type composition, and transepithelial electrical resistance varied among the donors and over time after air-lift. Cilia beating frequency increased in response to isoproterenol treatment in both culture types, independent of the donor. The cultures presented low basal cytochrome P450 (CYP) 1A1/1B1 activity, but 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment induced CYP1A1/1B1 activity regardless of the donor. In conclusion, lung epithelial cultures prepared from different donors present diverse morphology but similar functionality and metabolic activity, with certain variability in their response to stimulation.
ALI, airliquid interface; BTUB4, ß-tubulin 4; Bronchial culture; CBF, cilia beating frequency; CYP, cytochrome P450; Donor variability; Lung toxicology; MUC5AC, mucin 5AC; Organotypic; PBS, phosphate buffered saline; Small airway culture; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TEER, transepithelial electrical resistance
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Curr Res Toxicol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Suíça
País de publicação:
Holanda